Key Takeaways:
Arrowhead Pharmaceuticals' plozasiran cut triglycerides 79% and 81% in two Phase 3 trials, meeting all primary and secondary endpoints in severe hypertriglyceridemia.
"These results build on the compelling topline data and further strengthen our view that plozasiran has the potential to fundamentally change how severe hypertriglyceridemia is treated," Christopher Anzalone, president and chief executive officer at Arrowhead, said.
The data, presented at the European Society of Cardiology Congress 2026 in Munich, showed more than 90 percent of plozasiran-treated patients achieved triglycerides below 500 mg/dL at Month 12, and more than half fell below 150 mg/dL. In a prespecified pooled analysis, plozasiran reduced all acute pancreatitis events by 78 percent versus placebo (RR 0.22; 95% CI 0.07-0.67; p=0.008), a 4.1 percent absolute risk reduction with a number needed to treat of 24.
The results de-risk a key pipeline asset for Arrowhead, which plans to file a supplemental New Drug Application with the U.S. Food and Drug Administration by year-end 2026, using a Priority Review Voucher purchased Aug. 4. The company's REDEMPLO (plozasiran) is already approved for familial chylomicronemia syndrome in the U.S., Canada, China, Australia and the European Union.
Across the two studies, 757 patients were randomized to receive 25 mg plozasiran or placebo subcutaneously once every three months. Among patients with baseline triglycerides of at least 880 mg/dL, median reductions reached 85 percent in both trials. Plozasiran also produced significant reductions in APOC3, remnant cholesterol and non-HDL cholesterol.
The pancreatitis benefit grew with risk. Among patients with triglycerides of at least 500 mg/dL and a prior history of acute pancreatitis, plozasiran cut the event rate by 91 percent versus placebo (RR 0.09; 95% CI 0.02-0.41; p=0.002), a 34 percent absolute risk reduction with a number needed to treat of three. In the highest-risk subgroup, those with triglycerides above 880 mg/dL and prior pancreatitis, events fell 100 percent.
Safety was broadly comparable between groups. Treatment-emergent adverse events occurred in 73 percent of patients in both arms, with serious events in 8.3 percent of plozasiran-treated patients versus 10 percent on placebo. The most common adverse events were worsening glycemic control (14.3 percent versus 8.7 percent) and diarrhea (5.6 percent versus 3.2 percent). Three fatal events occurred in plozasiran-treated patients, all attributed to pre-existing disease and assessed as unrelated to treatment.
The efficacy and safety profile supports Arrowhead's plan to seek approval in the broader sHTG population, a market with limited treatment options. H.C. Wainwright raised its price target on Arrowhead to $120 from $115 in August, citing the pull-forward in the plozasiran launch timeline. Investors will watch the FDA filing, expected before the end of 2026, as the next catalyst for the stock.
This article is for informational purposes only and does not constitute investment advice.
